Most cancer therapies are severely limited by significant side effects due to non-specific tissue toxicity, and identification of novel agents that are selectively toxic to cancer cells or selectively sensitize tumors to treatment is a key goal in cancer research. A significant amount of work has focused on applying the specific binding activity of monoclonal antibodies to the development of tumor-specific therapies. Select antibodies such as trastuzumab (Herceptin®), rituximab (Rituxan®), and cetuximab (Erbitux®) have received approval for use in human cancer therapy, but all lack the ability to penetrate into cancer cells and are therefore limited to attacking targets located on the external surface of tumor cells.
A significant number of tumor-specific targets are located inside cells and nuclei, and numerous types of cancer are particularly vulnerable to treatments that inhibit DNA repair.
It is therefore an object of the invention to provide cell-penetrating antibodies, such as anti-DNA antibodies, that inhibit DNA repair.
It is a further object of the invention to provide compositions that increase the sensitivity of cancer cells to radiation therapy and/or chemotherapy.
It is a further object of the invention to provide cell-penetrating antibodies and derivatives thereof that are selectively toxic to cancer or other undesirable cells with pre-existing deficiencies in DNA repair, typically associated with familial syndromes due to mutations in DNA repair genes but also occurring sporadically with silencing or a mutation in DNA repair genes.
It is a further object of the invention to provide cell-penetrating antibodies and derivatives thereof that prevent or inhibit viral infection, integration, and/or replication by perturbing host DNA repair.